Rifapentine

Các tên gọi khác (3) :

3-(((4-Cyclopentyl-1-piperazinyl)imino)methyl)rifamycin
Cyclopentylrifampicin
Priftin (tn)

leprostatic agents, antibiotics antitubercular, antimycobacterials

Thuốc Gốc

Small Molecule

CAS: 61379-65-5

ATC: J04AB05

ĐG : Gruppo Lepetit SPA

CTHH: C₄₇H₆₄N₄O₁₂

PTK: 877.0307

Rifapentine is an antibiotic drug used in the treatment of tuberculosis. It inhibits DNA-dependent RNA polymerase activity in susceptible cells. Specifically, it interacts with bacterial RNA polymerase but does not inhibit the mammalian enzyme.

Nhận Dạng Quốc Tế & Đặc Tính Hóa Học

Công thức hóa học

C₄₇H₆₄N₄O₁₂

Phân tử khối

877.0307

Monoisotopic mass

876.452073532

InChI

InChI=1S/C47H64N4O12/c1-24-13-12-14-25(2)46(59)49-37-32(23-48-51-20-18-50(19-21-51)31-15-10-11-16-31)41(56)34-35(42(37)57)40(55)29(6)44-36(34)45(58)47(8,63-44)61-22-17-33(60-9)26(3)43(62-30(7)52)28(5)39(54)27(4)38(24)53/h12-14,17,22-24,26-28,31,33,38-39,43,53-57H,10-11,15-16,18-21H2,1-9H3,(H,49,59)/b13-12+,22-17+,25-14-,48-23+/t24-,26+,27+,28+,33-,38-,39+,43+,47-/m0/s1

InChI Key

InChIKey=WDZCUPBHRAEYDL-GZAUEHORSA-N

IUPAC Name

(7S,11S,12R,13S,14R,15R,16R,17S,18S)-26-[(E)-N-(4-cyclopentylpiperazin-1-yl)carboximidoyl]-2,15,17,27,29-pentahydroxy-11-methoxy-3,7,12,14,16,18,22-heptamethyl-6,23-dioxo-8,30-dioxa-24-azatetracyclo[23.3.1.1^{4,7}.0^{5,28}]triaconta-1,3,5(28),9,19,21,25(29),26-octaen-13-yl acetate

Traditional IUPAC Name

SMILES

CO[C@H]1\C=C\O[C@@]2(C)OC3=C(C2=O)C2=C(C(O)=C3C)C(O)=C(NC(=O)\C(C)=C/C=C/[C@H](C)[C@H](O)[C@@H](C)[C@@H](O)[C@@H](C)[C@H](OC(C)=O)[C@@H]1C)C(\C=N\N1CCN(CC1)C1CCCC1)=C2O

Độ hòa tan

2.13e-02 g/l

logP

logS

-4.6

pKa (strongest acidic)

7.01

pKa (Strongest Basic)

7.98

PSA

220.15 Å²

Refractivity

242 m³·mol^-1

Polarizability

93.14 Å³

Rotatable Bond Count

H Bond Acceptor Count

H Bond Donor Count

Physiological Charge

Number of Rings

Bioavailability

MDDR-Like Rule

true

Dược Lực Học : Rifapentine is an antibiotic that inhibits DNA-dependent RNA polymerase activity in susceptible cells. Specifically, it interacts with bacterial RNA polymerase but does not inhibit the mammalian enzyme. It is bactericidal and has a very broad spectrum of activity against most gram-positive and gram-negative organisms (including Pseudomonas aeruginosa) and specifically Mycobacterium tuberculosis. Because of rapid emergence of resistant bacteria, use is restricted to treatment of mycobacterial infections and a few other indications. Rifampin is well absorbed when taken orally and is distributed widely in body tissues and fluids, including the CSF. It is metabolized in the liver and eliminated in bile and, to a much lesser extent, in urine, but dose adjustments are unnecessary with renal insufficiency.

Cơ Chế Tác Dụng : Rifapentine is an antibiotic drug used in the treatment of tuberculosis. It inhibits DNA-dependent RNA polymerase activity in susceptible cells. Specifically, it interacts with bacterial RNA polymerase but does not inhibit the mammalian enzyme. Rifapentine has shown higher bacteriostatic and bactericidal activities especially against intracellular bacteria growing in human monocyte-derived macrophages. Rifapentine inhibits DNA-dependent RNA polymerase in susceptible strains of M. tuberculosis. Rifapentine acts via the inhibition of DNA-dependent RNA polymerase, leading to a suppression of RNA synthesis and cell death.

Dược Động Học :

▧ Absorption :
Rapidly and well absorbed from the gastrointestinal tract.
▧ Volume of Distribution :
* 70.2 ± 9.1 L
▧ Protein binding :
97.7% (bound to plasma proteins)
▧ Metabolism :
Hepatic
▧ Route of Elimination :
Following a single 600 mg oral dose of radiolabeled rifapentine to healthy volunteers (n=4), 87% of the total 14C rifapentine was recovered in the urine (17%) and feces (70%).
▧ Clearance :
* Apparent Oral cl=2.51 +/- 0.14 L/h [Male tuberculosis patients who received 600 mg rifapentine in combination with isoniazid, pyrazinamide and ethambutol] * Apparent Oral cl=1.69 +/- 0.41 L/h [Female tuberculosis patients who received 600 mg rifapentine in combination with isoniazid, pyrazinamide and ethambutol]

Chỉ Định : For the treatment of pulmonary tuberculosis.

Tương Tác Thuốc :

Abiraterone Strong CYP3A4 inducers may decrease levels of abiraterone. Monitor concomitant therapy closely.
Bromazepam Rifapentine may decrease the serum concentration of bromazepam by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of bromazepam if rifapentine is initiated, discontinued or dose changed.
Cabazitaxel Concomitant therapy with a strong CYP3A inducer may decrease concentrations of cabazitaxel. Avoid concomitant therapy.
Erlotinib Decreased levels/effect of erlotinib
Estradiol valerate/Dienogest Affects CYP3A4 metabolism, decreases or effects levels of Estradiol valerate/Dienogest.
Ethinyl Estradiol This product may cause a slight decrease of contraceptive effect
Methadone The rifamycin decreases the effect of methadone
Norethindrone This product may cause a slight decrease of contraceptive effect
Rilpivirine Strong inducers of CYP3A4 decrease the exposure of rilpivirine thus decreasing efficacy.
Roflumilast Affects CYP3A4 metabolism, decreases level or effect of roflumilast.
Telithromycin Rifapentine may decrease the plasma concentration of Telithromycin. Consider alternate therapy.
Temsirolimus Rifapentine may increase the metabolism of Temsirolimus decreasing its efficacy. Concomitant therapy should be avoided.
Terbinafine Rifapentine may increase the metabolism and clearance of Terbinafine. To avoid Terbinafine treatment failure, co-administration should be avoided.
Tipranavir Concomitant therapy may cause decreased Tipranavir and increased Rifapentine plasma concentrations.
Tramadol Rifapentine may decrease the effect of Tramadol by increasing Tramadol metabolism and clearance.
Trazodone The CYP3A4 inducer, Rifapentine, may decrease Trazodone efficacy by increasing Trazodone metabolism and clearance. Monitor for changes in Trazodone efficacy/toxicity if Rifapentine is initiated, discontinued or dose changed.
Tretinoin The strong CYP2C8 inducer, Rifapentine, may increase the metabolism and clearance of oral Tretinoin. Consider alternate therapy to avoid failure of Tretinoin therapy or monitor for changes in Tretinoin effectiveness and adverse/toxic effects if Rifapentine is initiated, discontinued or dose changed.
Vandetanib Decreases levels of vandetanib by affecting CYP3A4 metabolism. Contraindicated.
Vemurafenib Strong CYP3A4 inducers may decrease levels of vemurafenib. Monitor concomitant therapy closely.
Verapamil Rifapentine, a CYP3A4 inducer, may decrease the serum concentration of Verapamil by increasing its metabolism (particularly in the intestinal mucosa) and decreasing its absorption. Monitor for changes in the therapeutic/adverse effects of Verapamil if Rifapentine is initiated, discontinued or dose changed.
Voriconazole Rifapentine may decrease the serum concentration of voriconazole likely by increasing its metabolism via CYP3A enzymes. Voriconazole may increase the serum concentration of rifapentin likely by inhibiting its metabolism via CYP3A. Concomitant therapy is contraindicated.
Zidovudine Rifapentin may decrease the serum concentration of zidovudine by increasing its metabolism. Monitor for changes in the serum concentration and therapeutic and adverse effects of zidovudine if rifapentin is initiated, discontinued or dose changed.

Liều Lượng & Cách Dùng : Tablet - Oral

Dữ Kiện Thương Mại

Giá thị trường

Biệt dược thương mại : Priftin 150 mg tablet

Giá bán buôn : USD >3.96

Đơn vị tính : tablet

Nhà Sản Xuất

Công ty : Sanofi-Aventis

Sản phẩm biệt dược : Priftin

Đóng gói

Công ty : Gruppo Lepetit SPA
Công ty : Sanofi-Aventis Inc.

Website : http://www.sanofi-aventis.com

Tài Liệu Tham Khảo Thêm

drugbank

http://www.drugbank.ca/drugs/DB01201

PubChem Compound

http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=6323497

PubChem Substance

http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=46507322

KEGG Compound

http://www.genome.jp/dbget-bin/www_bget?cpd:C08059

KEGG Drug

http://www.genome.jp/dbget-bin/www_bget?drug:D00879

ChemSpider

http://www.chemspider.com/Chemical-Structure.4883449.html

National Drug Code Directory

http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/0088-2100-03

PharmGKB

http://www.pharmgkb.org/drug/PA164783809

Wikipedia

http://en.wikipedia.org/wiki/Rifapentine

RxList

http://www.rxlist.com/cgi/generic/priftin.htm

Drugs.com

http://www.drugs.com/cdi/rifapentine.html

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